title: Chemosensitivity and stratification by a five monoclonal antibody immunohistochemistry test in the NSABP B14 and B20 trials.
abstract: OBJECTIVE
  To test the association between risk stratification and outcome in a prospectively designed, blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor-expressing, node-negative samples from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials.
  
  
  METHODS
  Tissue arrays were stained by immunohistochemistry targeting p53, NDRG1, SLC7A5, CEACAM5, and HTF9C. Risk stratification was done using predefined scoring rules, algorithm for combining scores, and cutoff points for low-risk, moderate-risk, and high-risk patient strata.
  
  
  RESULTS
  In a univariate Cox model, this test was significantly associated with recurrence-free interval [HR, 1.3 (95% confidence interval, 1.1-1.6); P = 0.006]. In a multivariate model it contributed information independent of age, tumor size, and menopausal status (P = 0.007). The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73%, 86%, and 85% for the high-risk, moderate-risk, and low-risk groups (P = 0.001). The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23%, 10%, and 9% (P < 0.0001). Exploratory analysis in patients >/=60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78%, 89%, and 92%. Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy.
  
  
  CONCLUSIONS
  Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor-expressing, node-negative tamoxifen-treated patients. It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient populations. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients.
authors.affiliation: Applied Genomics, Inc., Burlingame, California 94010, USA. dross@applied-genomics.com
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Ross
authors.forename: Chung-Yeul
authors.initials: CY
authors.lastname: Kim
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.forename: Olga L
authors.initials: OL
authors.lastname: Bohn
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Beck
authors.forename: Brian Z
authors.initials: BZ
authors.lastname: Ring
authors.forename: Robert S
authors.initials: RS
authors.lastname: Seitz
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000368:Aged; D000465:Algorithms; D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010919:Placebos; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D016037:Single-Blind Method; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D027283:Large Neutral Amino Acid-Transporter 1; D010919:Placebos; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D016159:Tumor Suppressor Protein p53; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C527875:CEACAM5 protein, human; C495901:TP53 protein, human